반응 #474365

반응 방정식

N-(2-Bromo-6-fluorophenyl)-N′-[2-methoxy-5-(trifluoromethyl)phenyl]urea

triethylamine

tris(o-tolyl)phosphine

methyl acrylate

→

methyl {8-fluoro-3-[2-methoxy-5-(trifluoromethyl)phenyl]-2-oxo-1,2,3,4-tetrahydroquinazolin-4-yl}acetate

수율 75.0%

용매

Water

isobutyronitrile

반응 조건

후처리

1. 1
   온도cooled to room temperature
2. 2
   workup.STIRRINGthe mixture is stirred at room temperature for 1 h
3. 3
   여과the solid is filtered off with suction
4. 4
   세척washed with water/methanol (1:1, 2.5 l) and acetonitrile (850 ml)
5. 5
   기타The residue is dried overnight at 45° C. in the VDO to constant mass (21 h)

실험 절차

N-(2-Bromo-6-fluorophenyl)-N′-[2-methoxy-5-(trifluoromethyl)phenyl]urea (2.5 kg) is suspended in isobutyronitrile under a nitrogen atmosphere (9 l), then triethylamine (1.31 kg), bis(acetonitrile)dichloropalladium (64.9 g), tris(o-tolyl)phosphine (149 g) and methyl acrylate (1.59 kg) are added in this sequence. The resulting suspension is stirred at 90-100° C. for 22 h, then cooled to room temperature. Water (9 l) is added and the mixture is stirred at room temperature for 1 h, then the solid is filtered off with suction and washed with water/methanol (1:1, 2.5 l) and acetonitrile (850 ml). The residue is dried overnight at 45° C. in the VDO to constant mass (21 h) using entraining nitrogen. A total of 1.90 kg of methyl {8-fluoro-3-[2-methoxy-5-(trifluoromethyl)phenyl]-2-oxo-1,2,3,4-tetrahydroquinazolin-4-yl}acetate are obtained as a solid, corresponding to 74.9% of theory.

출처